Caspase-1-dependent inflammasomes mediate photoreceptor cell death in photo-oxidative damage-induced retinal degeneration
dc.contributor.author | Wooff, Yvette | |
dc.contributor.author | Fernando, Nilisha | |
dc.contributor.author | Wong, Josephine | |
dc.contributor.author | Dietrich, Catherine | |
dc.contributor.author | Aggio-Bruce, Riemke | |
dc.contributor.author | Chu-Tan, Joshua | |
dc.contributor.author | Robertson, Avril | |
dc.contributor.author | Doyle, Sarah | |
dc.contributor.author | Man, Si Ming | |
dc.contributor.author | Natoli, Riccardo | |
dc.date.accessioned | 2021-04-21T05:24:08Z | |
dc.date.available | 2021-04-21T05:24:08Z | |
dc.date.issued | 2020 | |
dc.date.updated | 2020-11-22T07:54:03Z | |
dc.description.abstract | Activation of the infammasome is involved in the progression of retinal degenerative diseases, in particular, in the pathogenesis of Age-Related Macular Degeneration (AMD), with NLRP3 activation the focus of many investigations. In this study, we used genetic and pharmacological approaches to explore the role of the infammasome in a mouse model of retinal degeneration. We identify that Casp1/11−/− mice have better-preserved retinal function, reduced infammation and increased photoreceptor survivability. While Nlrp3−/− mice display some level of preservation of retinal function compared to controls, pharmacological inhibition of NLRP3 did not protect against photoreceptor cell death. Further, Aim2−/−, Nlrc4−/−, Asc−/−, and Casp11−/− mice show no substantial retinal protection. We propose that CASP-1-associated photoreceptor cell death occurs largely independently of NLRP3 and other established infammasome sensor proteins, or that inhibition of a single sensor is not sufcient to repress the infammatory cascade. Therapeutic targeting of CASP-1 may ofer a more promising avenue to delay the progression of retinal degenerations. | en_AU |
dc.description.sponsorship | This work was funded by grants from the Ophthalmic Research Institute of Australia awarded to N.F (ORIA - New Investigator Grant, 2018), and the National Health and Medical Research Council of Australia (NHMRC: 1127705) and the ANU Translational Fellowship awarded to R.N. S.M.M. is supported by the Australian National University, Te Gretel and Gordon Bootes Medical Research Foundation, and the National Health and Medical Research Council of Australia under Project Grants (APP1141504, APP1146864, APP1162103 and APP1163358) and the R.D. Wright Career Development Fellowship (APP1162025). | en_AU |
dc.format.mimetype | application/pdf | en_AU |
dc.identifier.issn | 2045-2322 | en_AU |
dc.identifier.uri | http://hdl.handle.net/1885/230439 | |
dc.language.iso | en_AU | en_AU |
dc.provenance | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | en_AU |
dc.publisher | Nature Publishing Group | en_AU |
dc.relation | http://purl.org/au-research/grants/nhmrc/1127705 | en_AU |
dc.relation | http://purl.org/au-research/grants/nhmrc/1141504 | en_AU |
dc.relation | http://purl.org/au-research/grants/nhmrc/1146864 | en_AU |
dc.rights | © The Author(s) 2020 | en_AU |
dc.rights.license | Creative Commons Attribution 4.0 International License | en_AU |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_AU |
dc.source | Scientific Reports | en_AU |
dc.title | Caspase-1-dependent inflammasomes mediate photoreceptor cell death in photo-oxidative damage-induced retinal degeneration | en_AU |
dc.type | Journal article | en_AU |
dcterms.accessRights | Open Access | en_AU |
local.bibliographicCitation.lastpage | 20 | en_AU |
local.bibliographicCitation.startpage | 1 | en_AU |
local.contributor.affiliation | Wooff, Yvette, College of Health and Medicine, ANU | en_AU |
local.contributor.affiliation | Fernando, Nilisha, College of Health and Medicine, ANU | en_AU |
local.contributor.affiliation | Wong, Josephine, College of Health and Medicine, ANU | en_AU |
local.contributor.affiliation | Dietrich, Catherine, College of Health and Medicine, ANU | en_AU |
local.contributor.affiliation | Aggio-Bruce, Riemke, College of Health and Medicine, ANU | en_AU |
local.contributor.affiliation | Chu-Tan, Joshua, College of Health and Medicine, ANU | en_AU |
local.contributor.affiliation | Robertson, Avril, University of Queensland | en_AU |
local.contributor.affiliation | Doyle, Sarah, Trinity College Dublin | en_AU |
local.contributor.affiliation | Man, Si Ming, College of Health and Medicine, ANU | en_AU |
local.contributor.affiliation | Natoli, Riccardo, College of Health and Medicine, ANU | en_AU |
local.contributor.authoremail | u4672578@anu.edu.au | en_AU |
local.contributor.authoruid | Wooff, Yvette, u5978390 | en_AU |
local.contributor.authoruid | Fernando, Nilisha, u4672578 | en_AU |
local.contributor.authoruid | Wong, Josephine, u5808288 | en_AU |
local.contributor.authoruid | Dietrich, Catherine, u5796040 | en_AU |
local.contributor.authoruid | Aggio-Bruce, Riemke, u5333366 | en_AU |
local.contributor.authoruid | Chu-Tan, Joshua, u5025022 | en_AU |
local.contributor.authoruid | Man, Si Ming, u1036742 | en_AU |
local.contributor.authoruid | Natoli, Riccardo, u4100537 | en_AU |
local.description.notes | Imported from ARIES | en_AU |
local.identifier.absfor | 110906 - Sensory Systems | en_AU |
local.identifier.ariespublication | u6269649xPUB423 | en_AU |
local.identifier.citationvolume | 10 | en_AU |
local.identifier.doi | 10.1038/s41598-020-58849-z | en_AU |
local.identifier.scopusID | 2-s2.0-85079234574 | |
local.identifier.uidSubmittedBy | u6269649 | en_AU |
local.publisher.url | http://www.nature.com/srep/index.html | en_AU |
local.type.status | Published Version | en_AU |
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